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How New Genes Arise from Scratch

How New Genes Arise from Scratch Quanta Magazine


The standard gene duplication model explains many of the thousands of known gene families, but it has limitations. It implies that most gene innovation would have occurred very early in life’s history. According to this model, the earliest biological molecules 3.5 billion years ago would have created a set of genetic building blocks. Each new iteration of life would then be limited to tweaking those building blocks.

Yet if life’s toolkit is so limited, how could evolution generate the vast menagerie we see on Earth today? “If new parts only come from old parts, we would not be able to explain fundamental changes in development,” Bornberg-Bauer said.

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Life finds a way.

Certain genes, however, seem to defy that origin story. They have no known relatives, and they bear no resemblance to any other gene. They’re the molecular equivalent of a mysterious beast discovered in the depths of a remote rainforest, a biological enigma seemingly unrelated to anything else on earth.

The mystery of where these orphan genes came from has puzzled scientists for decades. But in the past few years, a once-heretical explanation has quickly gained momentum — that many of these orphans arose out of so-called junk DNA, or non-coding DNA, the mysterious stretches of DNA between genes. “Genetic function somehow springs into existence,” said David Begun, a biologist at the University of California, Davis.

Scientists have now catalogued a number of clear examples of de novo genes: 

A gene in yeast that determines whether it will reproduce sexually or asexually, a gene in flies and other two-winged insects that became essential for flight, and some genes found only in humans whose function remains tantalizingly unclear.

At the Society for Molecular Biology and Evolution conference last month, Albà and collaborators identified hundreds of putative de novo genes in humans and chimps — ten-fold more than previous studies — using powerful new techniques for analyzing RNA. Of the 600 human-specific genes that Albà’s team found, 80 percent are entirely new, having never been identified before.

Unfortunately, deciphering the function of de novo genes is far more difficult than identifying them. But at least some of them aren’t doing the genetic equivalent of twiddling their thumbs. Evidence suggests that a portion of de novo genes quickly become essential. About 20 percent of new genes in fruit flies appear to be required for survival. And many others show signs of natural selection, evidence that they are doing something useful for the organism.

In humans, at least one de novo gene is active in the brain, leading some scientists to speculate such genes may have helped drive the brain’s evolution. Others are linked to cancer when mutated, suggesting they have an important function in the cell. “The fact that being misregulated can have such devastating consequences implies that the normal function is important or powerful,” said Aoife McLysaght, a geneticist at Trinity College in Dublin who identified the first human de novo genes.

The Odds of Becoming a Gene

Scientists are testing computational approaches to determine how often random DNA sequences can be mutated into functional genes. Victor Luria, a researcher at Harvard, created a model using common estimates of the rates of mutation, recombination (another way of mixing up DNA) and natural selection. After subjecting a stretch of DNA as long as the human genome to mutation and recombination for 100 million generations, some random stretches of DNA evolved into active genes. If he were to add in natural selection, a genome of that size could generate hundreds or even thousands of new genes.

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